tbuckley/cabot-search huggingface dataset:
Gaps in adolescent and young adult oncology education during medical and pediatric hematology/oncology fellowship training.
Authors: Adam Duvall, Scott Moerdler, David R. Freyer, Allison Grimes, Brandon M. Hayes-Lattin, Varun Monga, Pinki Kumari Prasad, Michael Roth
Journal: Journal of Clinical Oncology (2022)

11026 Background: There are limited data on the extent of adolescent and young adult (AYA) education in pediatric and medical oncology fellowship programs. The purpose of this study was to assess the prevalence and content of AYA-focused training during pediatric and medical oncology fellowship and identify knowledge gaps for targeted educational curricular development. Methods: An anonymous, web-based survey for educators and trainees was developed, piloted and optimized by a study team comprising pediatric and adult oncologists. The survey contained questions on respondent demographics, AYA curriculum, provider comfort in managing specific AYA care domains, and priorities for future AYA educational content. In October 2021, email invitations containing the survey link were sent to program directors (PDs) and associate program directors (APDs) at 251 hematology/oncology fellowship programs (with 119 pediatric and 178 adult PDs/APDs) identified through the American Medical Association’s Fellowship and Residency Electronic Interactive Database Access. PDs were asked to participate and also distribute the survey to current fellows. The survey remained open for 3 months. Fisher’s exact test was used to assess for associations between discrete variables including amount of current education vs level of importance and demographic groups. Results: Respondents represented 69 programs (27%). There were 130 respondents who completed curriculum and demographic questions and 112 who completed detailed topic questions. Respondents comprised 51 PDs/APDs (32 pediatric and 19 adult) and 58 fellows (33 pediatric and 25 adult). 85% of PDs (44/51) do not have a formal AYA curriculum. Of these, 80% (35/44) offer some topic-specific lectures, while 20% (9/44) provide little/no education in any topics. For nearly all topics, at least 45% of respondents reported little/no education. Although onco-fertility and survivorship are the most frequently taught topics, 36% and 42% of respondents, respectively, reported little/no education in these areas. Substance abuse is least commonly taught. Both PDs and fellows believe that AYA topics are more important for inclusion in future curricula despite how infrequently they are currently taught (very/extremely important for inclusion vs moderate/great deal of current amount of education, p = 0.0001 for all topics). Overall, respondents indicated the most important topics for inclusion in fellowship curriculum were onco-fertility (82%), survivorship (78%), and communication (77%). Conclusions: These data highlight the large gap in hematology/oncology fellowship education in AYA topics and a paucity of formal educational curricula. Efforts are needed to provide both medical and pediatric oncology fellows with the knowledge and skills required to provide optimal care for AYAs.
A single-arm, phase 2 study of perioperative ipilimumab, nivolumab, and cryoablation in women with hormone receptor-negative, HER2-negative, early-stage/resectable breast cancer.
Authors: Heather L. McArthur, Elizabeth Anne Comen, Yolanda Bryce, Stephen Barnett Solomon, Jorge Henrique S. Leal, Christina DiLauro Abaya, Cristal Martinez, Reva K Basho, Dorothy J. Park, Philomena McAndrew, Brigid Larkin, William Mills, David B. Page, Staci L. Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha M. Reddy, Meredith Carter, Sujata Patil, Larry Norton
Journal: Journal of Clinical Oncology (2022)

TPS617 Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible pts are ≥18y, with ER &lt; 10%, PR &lt; 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 80 pts will be enrolled and treated with ipi/nivo/cryo followed by breast surgery and adjuvant nivo. Pts undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Clinical trial information: NCT03546686.
SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron’s impact in South African population cohorts
Authors: Kaiyuan Sun, Stefano Tempia, Jackie Kleynhans, Anne von Gottberg, Meredith L. McMorrow, Nicole Wolter, Jinal N. Bhiman, Jocelyn Moyes, Mignon du Plessis, Maimuna Carrim, Amelia Buys, Neil A. Martinson, Kathleen Kahn, Stephen Tollman, Limakatso Lebina, Floidy Wafawanaka, Jacques D. du Toit, Francesc Xavier Gómez-Olivé, Thulisa Mkhencele, Cécile Viboud, Cheryl Cohen
Journal: Science Translational Medicine (2022)

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.
Factors associated with receipt of second-line recurrent or metastatic cervical cancer treatment in the United States: A retrospective administrative claims analysis.
Authors: Kalyani Sonawane, Tara Castellano, Christina Washington, Turgay Ayer, Andy Surinach, Carol Kirshner, Jie Ting, Jagpreet Chhatwal, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2022)

5532 Background: There is limited real-world data on the proportion of eligible patients who received second-line (2L) treatment following progression on first-line (1L) systemic therapy for recurrent or metastatic cervical cancer (r/mCC). In addition, factors impacting selection of 2L are not well-understood. The objective of this study was to determine the prevalence and predictors of subsequent therapy among patients with 1L-treated r/mCC. Methods: We conducted a retrospective analysis of the 2015-2020 MarketScan claims database. Women ≥18 years of age with at least one inpatient claim or two outpatient claims with a diagnosis for malignant neoplasm of the cervix followed by 1L therapy codes were identified. The last recorded date of 1L treatment was assigned as the index date for each woman. Continuous enrollment criteria of minimum 3-month pre-index and 12-month post-index were applied. Women with claims for a new therapy after 60 days but no later than 365 days from the end of 1L treatment were identified as those who continued r/mCC treatment. We used descriptive statistics to examine the baseline characteristics of the final analytical cohort. A multivariable logistic regression model examined the factors associated with treatment discontinuation. All analyses were performed using SAS, Cary, NC. P-value was tested at 0.05. Results: A total of 1,080 patients with 1L-treated r/mCC were identified, of whom 384 met the study criteria. Post-1L treatment, 196 (51.0%) patients received a new therapy within a median duration of 122 days. A total 188 (49.0%) patients did not receive subsequent therapy. The geographic location of patient (identified based on census region as Northeast, Midwest, South, or West) and prior bevacizumab exposure were significant predictors of receiving subsequent therapy. Specifically, patients from the Midwest (odds ratio [OR] = 0.43; 95% CI: 0.23-0.84) and Southern (OR = 0.53; 95% CI: 0.29-0.96) regions had lower likelihood of receiving 2L treatment after 1L, compared to those living in the Northeast. Women without prior bevacizumab treatment were also less likely to receive subsequent therapy (OR = 0.65; 95% CI: 0.42-0.99). Age, type of health plan, and comorbidities were not associated with the likelihood of receiving subsequent treatment. Conclusions: Overall, nearly half of the 1L-treated r/mCC patients did not continue to 2L therapy, with findings showing treatment drop-off differing significantly by geographic region and prior treatment. Additional research and targeted outreach efforts are needed to understand geography-, population-, or practice-specific barriers impacting access to therapy among r/mCC patients.
Recurrent venous thromboembolism in cancer patients treated with direct oral anticoagulants.
Authors: Alice Talbot, Andrew Peter Dean, Ciara Brennan, Thomas Talbot, Sophia Angelov
Journal: Journal of Clinical Oncology (2022)

e13648 Background: Malignancy associated thrombosis places a significant clinical and financial burden on all major oncology services worldwide. Cancer patients are at an increased risk of thrombosis and large studies have suggested a subsequent increased mortality. (1) Some studies have recorded higher risk associated with certain chemotherapy regimens such as platinum-based agents and gemcitabine. (2) Guidelines for anticoagulation often recommend low molecular weight heparin (LMWH) as first line for malignancy associated thrombosis. (3) In recent years ASCO guidelines have added DOACs as an option for VTE treatment. (4) We herein describe eight cases of recurrent venous thromboembolism despite direct oral anticoagulation. Methods: Data was gathered from electronic patient records for cancer patients attending a single centre in Western Australia between 2016 and 2021. Radiology and medication records were used to confirm VTE diagnoses and subsequent treatment. This data was recorded on an excel file and analysed accordingly. Results: We identified 8 patients with recurrent VTE on DOACs. Median age of patients was 61 years (range 50-72). The most common associated malignancy was pancreatic cancer (n = 3). Other associated cancer types were ovarian (n = 2), lung adenocarcinoma (n = 2) and colorectal cancer(n = 1). Most patients had metastatic disease at time of first VTE(n = 5). The most common site of thrombosis was in the upper limb with 3 cases of initial VTE and 4 cases of recurrent VTE. All of these occurred in patients with peripherally inserted central catheters. (PICC) One patient had a left central retinal vein thrombosis resulting in complete loss of vision in that eye. All but one patient had received either platinum based chemotherapy or gemcitabine. Median time to initial thrombotic event was 4 months from diagnosis. Median time to recurrent thrombotic event was 3.5 months. Rivaroxaban was the most common DOAC used with initial VTE (n = 5). All other patients received apixaban (n = 3). All patients were switched to either LMWH (n = 6) or unfractionated heparin (n = 2) following recurrent VTE. 75% of patients did not have further thrombosis after switch to heparin. One patient had chronic thrombosis on subsequent scans and another patient had recurrent pulmonary embolism despite unfractionated heparin and vena cava filter insertion. Conclusions: Venous thromboembolism is a common complication of malignancy with significant associated morbidity and mortality. A high index of suspicion is needed in patients with clinical signs of recurrent VTE while on a DOAC, especially for those with PICCs. While DOACs are common for patient preference, the differing rates of VTE recurrences should be further investigated and considered in oncology prescribing practice going forward.
Metabolic regulation of endothelial reactive oxygen species production in obesity
Authors: C Padgett, A Speese, C Rosewater, Z Corley, J Mintz, D Fulton, D Stepp
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health (NIH) Introduction The prevalence of obesity continues to rise to unprecedented levels, and with it, a corresponding increase in the incidence of cardiovascular disease (CVD). While obesity is indeed accepted as one of the most prominent risk factors for CVD, the precise molecular mechanisms by which aberrant metabolism is linked to cardiovascular function remain incompletely understood. One prevailing hypothesis is that overproduction of reactive oxygen species (ROS) from increased metabolism significantly contributes to endothelial dysfunction, which precedes many cardiovascular events such as atherosclerosis and stroke. Purpose In this study, we hypothesized that a receptor for advanced glycation end products, Galectin-3 (GAL3), acts as a metabolic sensor and regulates endothelial ROS production in obesity. Methods Obese db/db mice were crossed with mice lacking GAL3, and endothelial gene expression, microvascular reactivity, and ROS production were assessed. Results We demonstrate that NADPH Oxidase I (NOX1), the predominant source of endothelial superoxide production, is down-regulated by GAL3 deletion, thereby rescuing endothelial function and ameliorating endothelial ROS production in obesity. Furthermore, we demonstrate that GAL3-mediated NOX1 over-expression is amenable to improvements in metabolic status, such as lowering blood glucose with metformin, improving glucose handling by augmenting muscle mass, or improving insulin signaling through deletion of Protein Tyrosine Phosphatase 1B (PTP1B). Conclusion Taken together, these data demonstrate that the overproduction of superoxide by endothelial NOX1 is regulated by the metabolic sensor GAL3 in obesity, leading to endothelial dysfunction and CVD. This pathway presents an attractive target for therapeutic intervention to break the link between aberrant metabolism in obesity and its corresponding vascular pathologies.
Poverty, race, ethnicity, and survival among U.S. children with non-metastatic osteosarcoma treated on EURAMOS-1: A report from the Children’s Oncology Group.
Authors: Lenka Anne Skaidrite Ilcisin, Ruxu Han, Mark D. Krailo, Richard Greg Gorlick, Helen Ruth Nadel, Odion Binitie, Katherine A. Janeway, Kira Bona
Journal: Journal of Clinical Oncology (2022)

10004 Background: Children living in poverty and those who identify as a race/ethnicity other than non-Hispanic White experience higher rates of relapse and lower overall survival across many pediatric cancers. Racial, ethnic and socioeconomic disparities have not been comprehensively investigated in osteosarcoma. We leveraged data from US-enrolled patients on the recent international EURAMOS-1 trial to investigate disparities in survival outcomes. Aim: Identify if race/ethnicity, household or neighborhood poverty exposure are associated with event-free survival (EFS) or overall survival (OS) in patients with non-metastatic osteosarcoma enrolled at a US-center on EURAMOS-1. Methods: Retrospective cohort study of US patients aged 5-21 years enrolled on EURAMOS-1 with a diagnosis of non-metastatic, primary osteosarcoma. Poverty was the primary exposure defined at the household- (sole coverage with Medicaid or CHIP public insurance versus other) and neighborhood- (Census-defined high-poverty ZIP code with &gt;20% of residents living at &lt;100% Federal Poverty Level vs other) levels. Race and ethnicity were categorized to reflect structural inequities and historically marginalized populations, as Hispanic, non-Hispanic Black (NHB), non-Hispanic Other (NHO), and non-Hispanic White (NHW). OS and EFS as a function of time from trial enrollment were estimated using the Kaplan-Meier method. Hypotheses of associations between risks for EFS-event, death and post-relapse death with poverty-exposures and race/ethnicity were assessed using log-rank tests. Statistical comparisons were performed excluding patients with missing values for the exposures considered. P-values &lt;=0.05 were considered significant. Results: Among 758 patients, 27% were household poverty-exposed and 29% were neighborhood-poverty exposed. Twenty-one percent of children identified as Hispanic, 17% NHB, 5% NHO and 57% NHW. Neither household- or neighborhood-poverty, nor race/ethnicity were significantly associated with risks for EFS-event or death. Post-relapse risk for death differed significantly across race/ethnicity with NHB at greatest risk compared to others (4-Year post-relapse survival 35.7% Hispanic vs. 13.0% NHB vs. 43.8% NHO vs 38.9% NHW; p=0.0046). Conclusions: Neither poverty-exposures nor race/ethnicity were associated with EFS or OS in this COG trial-enrolled cohort, suggesting equitable outcomes following standardized therapy. Despite this, non-Hispanic Black children experienced significantly inferior post-relapse survival. Investigation of mechanisms driving these post-relapse disparities, including inequities in health care delivery and access to post-relapse trial-enrollment, are paramount to ensure equity in outcomes for all children with cancer.
Prognostic impact of t(11;14) on PFS1 among patients with myeloma receiving triplet induction therapy.
Authors: Shama Pirmohammed, Nisha Joseph, Craig C. Hofmeister, Leonard T. Heffner, Vikas Anand Gupta, Lawrence Boise, Madhav V. Dhodapkar, Sagar Lonial, Ajay K. Nooka, Jonathan L. Kaufman
Journal: Journal of Clinical Oncology (2022)

8064 Background: Presence of t(11;14) on plasma cells by FISH or metaphase cytogenetics is considered a standard-risk prognostic factor per IMWG risk-stratification. However, recent studies suggest inferior PFS and OS observed among t(11;14) patients relative to the standard-risk myeloma patients. In the context of the ongoing trials of BCL-2 inhibitors (venetoclax) among t(11;14) relapse/refractory myeloma patients yielding response rates closer to 90%, we review the prognostic impact of t(11;14) on PFS. These results may have implications for earlier incorporation of BCL-2 inhibitors among t(11;14) myeloma patients. Methods: Among the 1000 consecutive newly diagnosed myeloma patients uniformly treated with RVD induction therapy from January 2008 until August 2016, we have information on FISH probes for t(11;14) tested for 869 patients [121 - t(11;14) and 748 – no t(11;14)]. First, we explore the frequency of IMWG defined concomitant high-risk cytogenetic characteristics [del 17p, t(4;14), t (14;16)]. Next, we create a synthetic control cohort that received maintenance, and excluded patients exhibiting high-risk features to evaluate the relative prognostication conferred by presence of t(11;14). Median follow up was 91 months. Demographic and outcomes data were collected from IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: Median age is 61.2 years (range 16.3-79.83). 34% of the patients are above the age of 65. Men (14.1% vs 11.7%, p = NS) and blacks had higher rates of t(11;14) (16.1% vs 11.1%, p = 0.028). 17 (14%) had concomitant high-risk features – 4 (3.3%) had t(4;14), 3 (2.5%) had t(14;16) and 11 (9.1%) had del17p. Interestingly, the rates of amplification of 1q (26.1% vs 14.9%, p = 0.002), and del13 (34.7% vs 24.4%, p = 0.015) were higher among t(11;14) patients. Compared to the synthetic cohort, the post-induction and post-transplant responses were lower for t(11;14) patients as summarized in table 1. ≥VGPR for t(11;14) vs no t(11;14) post-induction were 48.2% vs 71.5% p &lt; 0.001 and post-transplant were 83.1% vs 92.8% p = 0.001, respectively. The median progression-free survival for the t(11;14) and non-t(11;14) groups were 61.4 months (95% confidence interval (CI), 49.13-73.67) and 82.56 months (95% CI, 70.47-94.65) months, respectively (p = 0.002). Conclusions: Even with the use of modern day induction regimens and transplant, patients with t(11;14) seem to have inferior response rates compared to the other standard-risk myelomas. The lower rates of ≥VGPR post-induction and the shorter median PFS suggests BCL-2 inhibitors such as venetoclax may be incorporated earlier in myeloma treatments to improve the outcomes of t(11;14) patients on par with the other standard-risk myeloma patients.
Differences in environmental stability among SARS-CoV-2 variants of concern: both omicron BA.1 and BA.2 have higher stability
Authors: Ryohei Hirose, Yoshito Itoh, Hiroshi Ikegaya, Hajime Miyazaki, Naoto Watanabe, Takuma Yoshida, Risa Bandou, Tomo Daidoji, Takaaki Nakaya
Journal: Clinical Microbiology and Infection (2022)

The increased infectivity and transmissibility of SARS-CoV-2 variants of concern (VOCs) could cause significant human and economic damage. Hence, understanding their characteristics is crucial to control infection. We evaluated the environmental stability of the Wuhan strain and all VOCs (Alpha, Beta, Gamma, Delta, Omicron BA.1, and Omicron BA.2 variants) on plastic and human skin surfaces and their disinfection efficacy.To evaluate environmental stability, residual virus titres on plastic and human skin surfaces were measured over time. Their survival time and half-life were calculated using regression analysis. The effectiveness of ethanol-based disinfectants at different concentrations was determined by in vitro and ex vivo evaluations.On plastic and skin surfaces, the Alpha, Beta, Delta, and Omicron variants exhibited approximately two-fold longer survival times than the Wuhan strain; the Omicron variants had the longest survival time. The median survival times of the Wuhan strain and the Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) variants on human skin surface were 8.6, 19.6, 19.1, 11.0, 16.8, 21.1, and 22.5 h, respectively. The in vitro evaluation showed that the Wuhan strain and the Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) variants were completely inactivated within 15 s by 32.5%, 35%, 35%, 32.5%, 35%, 40%, and 40% ethanol, respectively. However, all viruses on human skin were completely inactivated by exposure to 35% ethanol for 15 s.SARS-CoV-2 VOCs, especially the Omicron variants, have higher environmental stability than the Wuhan strain, increasing their transmission risk and contributing to their spread.